Wu Zhimin, Duan Manzhen, Xiong Di, Zhang Can Yang
School of Chemical Engineering, Xiangtan University, Xiangtan 411105, China.
Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA 99210, USA.
Pharmaceutics. 2019 Nov 20;11(12):620. doi: 10.3390/pharmaceutics11120620.
It is of great significance to study the structure property and self-assembly of amphiphilic block copolymer in order to effectively and efficiently design and prepare drug delivery systems. In this work, dissipative particle dynamics (DPD) simulation method was used to investigate the structure property and self-assembly ability of pH-responsive amphiphilic block copolymer poly(methyl methacrylatemethacrylic acid)poly(aminoethyl methacrylate) (poly(MMAMAA)PAEMA). The effects of different block ratios (hydrophilic PAEMA segment and pH-sensitive PMAA segment) in copolymer on self-assembly and drug loading capacity including drug distribution were extensively investigated. The increase of hydrophilic PAEMA facilitated the formation of a typical core-shell structure as well as a hydrophobic PMAA segment. Furthermore, the optimal drug-carrier ratio was confirmed by an analysis of the drug distribution during the self-assembly process of block copolymer and model drug Ibuprofen (IBU). In addition, the drug distribution and nanostructure of IBU-loaded polymeric micelles (PMs) self-assembled from precise block copolymer (PMMAPMAAPAEMA) and block copolymer (poly(MMAMAA)PAEMA) with random pH-responsive/hydrophobic structure were evaluated, showing that almost all drug molecules were encapsulated into a core for a random copolymer compared to the analogue. The nanostructures of IBU-loaded PMs at different pH values were evaluated. The results displayed that the nanostructure was stable at pH < pK and anomalous at pH > pK which indicated drug release, suggesting that the PMs could be used in oral drug delivery. These findings proved that the amphiphilic block copolymer P(MMAMAA)PAEMA with random structure and pH-sensitivity might be a potential drug carrier. Moreover, DPD simulation shows potential to study the structure property of PMs self-assembled from amphiphilic block copolymer.
研究两亲性嵌段共聚物的结构性质和自组装对于有效且高效地设计和制备药物递送系统具有重要意义。在本工作中，采用耗散粒子动力学（DPD）模拟方法研究了pH响应性两亲性嵌段共聚物聚（甲基丙烯酸甲酯 - 甲基丙烯酸） - 聚（甲基丙烯酸氨基乙酯）（聚（MMAMA） - PAEMA）的结构性质和自组装能力。广泛研究了共聚物中不同嵌段比例（亲水性PAEMA链段和pH敏感的PMAA链段）对自组装和载药能力（包括药物分布）的影响。亲水性PAEMA的增加促进了典型核壳结构以及疏水性PMAA链段的形成。此外，通过分析嵌段共聚物与模型药物布洛芬（IBU）自组装过程中的药物分布，确定了最佳的药物 - 载体比例。此外，还评估了由具有精确结构的嵌段共聚物（PMMAPMAAPAEMA）和具有随机pH响应/疏水结构的嵌段共聚物（聚（MMAMA） - PAEMA）自组装而成的载药聚合物胶束（PMs）的药物分布和纳米结构，结果表明与类似物相比，对于无规共聚物，几乎所有药物分子都被包裹在核中。评估了不同pH值下载药PMs的纳米结构。结果表明，纳米结构在pH < pK时稳定，在pH > pK时异常，这表明药物释放，表明PMs可用于口服药物递送。这些发现证明具有无规结构和pH敏感性的两亲性嵌段共聚物P（MMAMA） - PAEMA可能是一种潜在的药物载体。此外，DPD模拟显示出研究由两亲性嵌段共聚物自组装而成的PMs结构性质的潜力。
